UniProt functional annotation for O43924



	UniProt functional annotation for O43924

UniProt code: O43924.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Promotes the release of prenylated target proteins from cellular membranes (PubMed:9712853). Modulates the activity of prenylated or palmitoylated Ras family members by regulating their subcellular location (PubMed:22002721, PubMed:23698361). Required for normal ciliary targeting of farnesylated target proteins, such as INPP5E (PubMed:24166846). Modulates the subcellular location of target proteins by acting as a GTP specific dissociation inhibitor (GDI) (By similarity). Increases the affinity of ARL3 for GTP by several orders of magnitude. Stabilizes ARL3-GTP by decreasing the nucleotide dissociation rate (By similarity). {ECO:0000250|UniProtKB:O55057, ECO:0000269|PubMed:10518933, ECO:0000269|PubMed:22002721, ECO:0000269|PubMed:23559067, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:24166846, ECO:0000269|PubMed:9712853}.

Subunit: Interacts with the prenylated catalytic subunits of PDE6, an oligomer composed of two catalytic chains (PDE6A and PDE6B) and two inhibitory chains (gamma); has no effect on enzyme activity but promotes the release of the prenylated enzyme from cell membrane (By similarity). Interacts with prenylated GRK1 and GRK7 (By similarity). Interacts with prenylated Ras family members, including RAP2A and RAP2C (By similarity). Interacts with prenylated RHEB and NRAS (PubMed:22002721). Interacts with prenylated HRAS and KRAS. Interacts with RAB13 (prenylated form); dissociates RAB13 from membranes (PubMed:9712853). Interacts with prenylated INPP5E (PubMed:24166846). Interacts with RPGR (PubMed:9990021, PubMed:24166846, PubMed:23559067). Interacts with ARL2 (PubMed:24166846, PubMed:22002721). Interacts with ARL3; the interaction occurs specifically with the GTP-bound form of ARL3 (PubMed:24166846). Interaction with ARL2 and ARL3 promotes release of farnesylated cargo proteins (PubMed:22002721). {ECO:0000250|UniProtKB:O55057, ECO:0000250|UniProtKB:Q95142, ECO:0000269|PubMed:10518933, ECO:0000269|PubMed:11980706, ECO:0000269|PubMed:22002721, ECO:0000269|PubMed:23559067, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:24166846, ECO:0000269|PubMed:9990021}.

Subcellular location: Cytoplasm, cytosol {ECO:0000269|PubMed:22002721, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:9712853}. Cytoplasmic vesicle membrane {ECO:0000269|PubMed:9712853}; Peripheral membrane protein {ECO:0000269|PubMed:9712853}. Cytoplasm, cytoskeleton, cilium basal body {ECO:0000269|PubMed:24166846}.

Tissue specificity: Widely expressed. Detected in various tissues including spleen, prostate gland, testis, ovary, small intestine, colon, retina, and peripheral blood. {ECO:0000269|PubMed:9712853}.

Disease: Joubert syndrome 22 (JBTS22) [MIM:615665]: A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. {ECO:0000269|PubMed:24166846}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the PDE6D/unc-119 family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Promotes the release of prenylated target proteins from cellular membranes (PubMed:9712853). Modulates the activity of prenylated or palmitoylated Ras family members by regulating their subcellular location (PubMed:22002721, PubMed:23698361). Required for normal ciliary targeting of farnesylated target proteins, such as INPP5E (PubMed:24166846). Modulates the subcellular location of target proteins by acting as a GTP specific dissociation inhibitor (GDI) (By similarity). Increases the affinity of ARL3 for GTP by several orders of magnitude. Stabilizes ARL3-GTP by decreasing the nucleotide dissociation rate (By similarity). {ECO:0000250\|UniProtKB:O55057, ECO:0000269\|PubMed:10518933, ECO:0000269\|PubMed:22002721, ECO:0000269\|PubMed:23559067, ECO:0000269\|PubMed:23698361, ECO:0000269\|PubMed:24166846, ECO:0000269\|PubMed:9712853}.


Subunit:		Interacts with the prenylated catalytic subunits of PDE6, an oligomer composed of two catalytic chains (PDE6A and PDE6B) and two inhibitory chains (gamma); has no effect on enzyme activity but promotes the release of the prenylated enzyme from cell membrane (By similarity). Interacts with prenylated GRK1 and GRK7 (By similarity). Interacts with prenylated Ras family members, including RAP2A and RAP2C (By similarity). Interacts with prenylated RHEB and NRAS (PubMed:22002721). Interacts with prenylated HRAS and KRAS. Interacts with RAB13 (prenylated form); dissociates RAB13 from membranes (PubMed:9712853). Interacts with prenylated INPP5E (PubMed:24166846). Interacts with RPGR (PubMed:9990021, PubMed:24166846, PubMed:23559067). Interacts with ARL2 (PubMed:24166846, PubMed:22002721). Interacts with ARL3; the interaction occurs specifically with the GTP-bound form of ARL3 (PubMed:24166846). Interaction with ARL2 and ARL3 promotes release of farnesylated cargo proteins (PubMed:22002721). {ECO:0000250\|UniProtKB:O55057, ECO:0000250\|UniProtKB:Q95142, ECO:0000269\|PubMed:10518933, ECO:0000269\|PubMed:11980706, ECO:0000269\|PubMed:22002721, ECO:0000269\|PubMed:23559067, ECO:0000269\|PubMed:23698361, ECO:0000269\|PubMed:24166846, ECO:0000269\|PubMed:9990021}.
Subcellular location:		Cytoplasm, cytosol {ECO:0000269\|PubMed:22002721, ECO:0000269\|PubMed:23698361, ECO:0000269\|PubMed:9712853}. Cytoplasmic vesicle membrane {ECO:0000269\|PubMed:9712853}; Peripheral membrane protein {ECO:0000269\|PubMed:9712853}. Cytoplasm, cytoskeleton, cilium basal body {ECO:0000269\|PubMed:24166846}.
Tissue specificity:		Widely expressed. Detected in various tissues including spleen, prostate gland, testis, ovary, small intestine, colon, retina, and peripheral blood. {ECO:0000269\|PubMed:9712853}.
Disease:		Joubert syndrome 22 (JBTS22) [MIM:615665]: A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. {ECO:0000269\|PubMed:24166846}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the PDE6D/unc-119 family. {ECO:0000305}.